The present invention is directed to the field of organ preservation, and in particular, to an apparatus and method of maintaining the viability of animal organs, tissue and various other animal parts.
There is a strong emphasis on maintaining the viability of animal organs, and in particular human organs, for long periods of time to increase the use of such organs for transplantation and medical research. Specifically, the ability to perform a transplant operation is dependent upon the availability of suitable organs. The availability of such organs is particularly dependent upon maintaining the viability of an organ after removal from its donor, and more so if the organ must be transported over a great distance to the intended recipient.
There is also a critical need to maintain the viability of organs for performing medical experiments on such organs. For example, it is safer to test new drugs on particular human organs than on humans themselves. However, in order to do such testing the organs, which have been removed from the donor body, must be maintained not only viable, but also in as close as possible to its natural state.
Presently available apparatus and methods take a number of different approaches to maintain the viability of animal organs for such uses. However, such apparatus are designed to minimize the normal metabolic functions of the organ. For example, presently available apparatus either completely freeze the organ, or lower the organ temperature to such a degree that there is a substantial suspension of the normal metabolic activities of the organ. In order to enhance the viability of the organ a nutrient solution, perfusate, is circulated through the organ.
Specific examples of these types of methods include maintaining the organ in a balanced electrolyte bath (hyperthermia), maintaining the organ at normal temperatures while storing the organ in an electrolyte bath under a positive pressure oxygen atmosphere (hypobaric) or pumping an oxygenated nutrient medium (a perfusate) through the organ to be preserved (perfusion). Apparatus which maintain an organ viability in accordance with one or more of these methods are disclosed in U.S. Pat. Nos. 3,406,531 (Swenson et al); 3,738,914 (Thorne et al); 3,545,221 (Swenson et al); 3,753,865 Belzer et al); 3,607,646 de Roissart); 3,772,153 (de Roissart) with the disclosure of all such references being incorporated herein by reference.
Thus, while presently available apparatus are suitable for maintaining the viability of organs, such apparatus can not maintain the normal metabolic activities of the organ. This limits the usefulness of such apparatus in drug research, since such research requires the ability to observe the effect that a drug will have upon the metabolic activities of the organ. The inability of presently available apparatus to maintain an organ in a state where the normal metabolic activities are allowed to continue has now been determined to be a function of numerous factors. In particular, it has now been determined that the temperature at which the organ is maintained as well as regulating the electrical potential of the organ is critical.
Previous apparatus have not attempted to regulate the electrical potential of the organs. It is well known that individual cells possess transmembrane potentials. That is, in each cell there is a distribution of electrical potential across the cell membrane. This potential exists because of the distribution of various types of ions on opposing sides of the cell membrane. That is, the distribution of one or more type of ions inside the cell membrane as opposed to the distribution of other types of ions outside the cell membrane causes an overall electrical potential or polarization of electrical charge along the cell membrane.
When this potential becomes sufficiently altered the cell is said to be excited. Specifically, when a resting cell is depolarized to a critical level, known as the threshold, the membrane becomes permeable and a regenerative inward current causes an action potential. The result is a variance in the cell membrane voltage which directly affects the activity of that cell.
The activity of various cells, as a function of the regulation of this transmembrane potential, will have a profound effect upon the organ in which the cells are located. That is, the metabolic activities of an organ is a function of the activity of individual cells. Thus, the regulation of the cellular transmembrane potential will directly affect the metabolic activity of the organ.
For example, the activity of muscle cells is affected by this transmembrane potential. Those organs which are characteristically dependent upon muscle cell activity, e.g., the heart, depend upon the regulation of this cellular transmembrane potential to control the muscular tissue activity. Nerve cells are another example of cells which are particularly affected by the regulation of this transmembrane potential. All organs depend to a varying extent upon the functioning of nerve cells and are thus susceptible to a depolarization of such cells.
This transmembrane potential can be affected by many conditions. For example, the concentration of various ions in a cell will affect the polarization of this membrane potential. Fluctuations in the cell physical environment will also have a profound effect upon the polarization of this transmembrane potential. In particular, temperature and electrical stimulation will affect this potential.
It can thus be seen that presently available apparatus are not suited for maintaining the viability of organs in a state whereby the organ maintains its normal metabolic activities. Furthermore, some presently available apparatus directly affect the transmembrane potential by freezing the organ. It would thus be beneficial to provide an apparatus which can store an organ in an environment as close as possible to its natural state. This includes not only maintaining such an organ providing the organ with sufficient nutrients and oxygen as previous apparatus have accomplished, but also by monitoring and regulating the temperature and transmembrane potential of the organ.